Dysbindin, Syncoilin, and β-Synemin mRNA Levels in Dystrophic Muscles

Wakayama, Yoshihiro; Matsuzaki, Yoko; Yamashita, Sumimasa; Inoue, Masahiko; Jimi, Takahiro; Hara, Hajime; Unaki, Akihiko; Iijima, Satoshi; Masaki, Hisatsugu

doi:10.3109/00207450903279717

Cited by 4 publications

(3 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, SNPs in this gene have been extensively associated with schizophrenia [21-23]. In vitro studies indicated dysbindin as a binding partner of several proteins with a suggested role in muscular physiology [24-26], and increased dysbindin transcript and protein levels were measured in muscle biopsies from individuals and mice with Duchenne Muscular Dystrophy (DMD; MIM 310200) [27,28]. However, muscle pathology was not reported in mutant Dtnbp1 mice [16], and not detected in BLOC-1-deficient mice [29].…”

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability

Barøy

Misceo

Strømme

et al. 2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundNineteen patients with deletions in chromosome 6p22-p24 have been published so far. The syndromic phenotype is varied, and includes intellectual disability, behavioural abnormalities, dysmorphic features and structural organ defects. Heterogeneous deletion breakpoints and sizes (1–17 Mb) and overlapping phenotypes have made the identification of the disease causing genes challenging. We suggest JARID2 and ATXN1, both harbored in 6p22.3, as disease causing genes.Methods and resultsWe describe five unrelated patients with de novo deletions (0.1-4.8 Mb in size) in chromosome 6p22.3-p24.1 detected by aCGH in a cohort of approximately 3600 patients ascertained for neurodevelopmental disorders. Two patients (Patients 4 and 5) carried non-overlapping deletions that were encompassed by the deletions of the remaining three patients (Patients 1–3), indicating the existence of two distinct dosage sensitive genes responsible for impaired cognitive function in 6p22.3 deletion-patients. The smallest region of overlap (SRO I) in Patients 1–4 (189 kb) included the genes JARID2 and DTNBP1, while SRO II in Patients 1–3 and 5 (116 kb) contained GMPR and ATXN1. Patients with deletion of SRO I manifested variable degrees of cognitive impairment, gait disturbance and distinct, similar facial dysmorphic features (prominent supraorbital ridges, deep set eyes, dark infraorbital circles and midface hypoplasia) that might be ascribed to the haploinsufficiency of JARID2. Patients with deletion of SRO II showed intellectual disability and behavioural abnormalities, likely to be caused by the deletion of ATXN1. Patients 1–3 presented with lower cognitive function than Patients 4 and 5, possibly due to the concomitant haploinsufficiency of both ATXN1 and JARID2. The chromatin modifier genes ATXN1 and JARID2 are likely candidates contributing to the clinical phenotype in 6p22-p24 deletion-patients. Both genes exert their effect on the Notch signalling pathway, which plays an important role in several developmental processes.ConclusionsPatients carrying JARID2 deletion manifested with cognitive impairment, gait disturbance and a characteristic facial appearance, whereas patients with deletion of ATXN1 seemed to be characterized by intellectual disability and behavioural abnormalities. Due to the characteristic facial appearance, JARID2 haploinsufficiency might represent a clinically recognizable neurodevelopmental syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability

Barøy

Misceo

Strømme

et al. 2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Third, elevated dysbindin is a common pathogenic factor in both the DMD (and BMD) and LGMD2H contexts [ 58 , 87 , 151 , 152 , 153 ]. Knockdown of TRIM32 in C2C12 myoblasts using siRNA resulted in elevated levels of dysbindin [ 58 ].…”

Section: Trim32 and Dmdmentioning

confidence: 99%

“…Dysbindin is a member of the dystrophin-associated protein complex, and the dysbindin level was increased in the TA muscle of mdx mice [ 151 ]. Upregulation of dysbindin expression at the mRNA level was observed in muscle biopsy samples from DMD patients compared with samples from healthy individuals [ 152 ]. In biopsy samples of the femoral quadriceps muscle from patients with DMD or BMD, TRIM32 expression was downregulated in necrotic muscle fibers compared with regenerating muscle fibers [ 153 ].…”

Section: Trim32 and Dmdmentioning

confidence: 99%

Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Jeong,

Choi,

Kim

et al. 2023

Cells

View full text Add to dashboard Cite

Tripartite motif-containing protein 32 (TRIM32) is a member of the tripartite motif family and is highly conserved from flies to humans. Via its E3 ubiquitin ligase activity, TRIM32 mediates and regulates many physiological and pathophysiological processes, such as growth, differentiation, muscle regeneration, immunity, and carcinogenesis. TRIM32 plays multifunctional roles in the maintenance of skeletal muscle. Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, including limb–girdle muscular dystrophy type 2H (LGMD2H). LGMD2H-causing genetic variations of TRIM32 occur most frequently in the C-terminal NHL (ncl-1, HT2A, and lin-41) repeats of TRIM32. LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. Surprisingly, most patients with LGMD2H show minimal or no dysfunction in other tissues or organs, despite the broad expression of TRIM32 in various tissues. This suggests more prominent roles for TRIM32 in skeletal muscle than in other tissues or organs. This review is focused on understanding the physiological roles of TRIM32 in skeletal muscle, the pathophysiological mechanisms mediated by TRIM32 genetic variants in LGMD2H patients, and the correlations between TRIM32 and Duchenne muscular dystrophy (DMD).

show abstract

Synemin down-regulation in human hepatocellular carcinoma does not destabilize cytoskeletons in vivo

Liu

Cheng

Lai

et al. 2011

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Dysbindin, Syncoilin, and β-Synemin mRNA Levels in Dystrophic Muscles

Cited by 4 publications

References 32 publications

Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability

Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability

Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Synemin down-regulation in human hepatocellular carcinoma does not destabilize cytoskeletons in vivo

Contact Info

Product

Resources

About